Oral ivermectin versus 5% permethrin cream to treat children and adults with classic scabies: multicentre, assessor blinded, cluster randomised clinical trial

Abstract

Objective: To investigate whether oral ivermectin or topical 5% permethrin can clinically cure scabies in index cases and in members of their households.

Design: Multicentre, assessor blinded, cluster randomised clinical trial.

Setting: 28 French hospitals, 19 January 2016 to 16 December 2021.

Participants: Index cases; adults and children weighing >15 kg with scabies, confirmed by dermoscopy.

Interventions: Index cases were randomly assigned to the ivermectin group or permethrin group (1:1 ratio). Each member of the cluster, defined as the household of each index case, received the same treatment as the index case, except for children weighing <15 kg who were prescribed topical 5% permethrin. All participants received oral ivermectin 200 µg/kg or 5% permethrin cream on day 0 and day 10. Permethrin cream was applied to the whole body, from head to toe.

Main outcome measures: The primary outcome was clinical cure of the cluster on day 28 (ie, disappearance of clinical signs and symptoms of scabies for all cluster members). Secondary outcomes were index case and individual level analyses and safety. Dermatologists were used as assessors and were masked to the treatment.

Results: 507 participants in 142 households (clusters) were treated with ivermectin and 568 participants in 147 households received permethrin. Cluster level cure rates were 71.8% versus 88.5% (-16.7 percentage point difference, 95% confidence interval (CI) -26.3 to -7.1) for ivermectin versus permethrin. Secondary outcome percentage point differences also showed the inferiority of ivermectin compared with 5% permethrin for index cases (76.6% v 91.5%; percentage point difference -14.9, 95% CI -23.6 to -6.2) and participants (85.3% v 94.2%; -9.2 percentage point difference, -14.9 to -3.5). Intraclass correlation coefficients were higher for permethrin than ivermectin for all clusters (0.68, 95% CI 0.61 to 0.75 v 0.46, 0.37 to 0.56) and for cluster size >1 (0.67, 0.60 to 0.74 v 0.47, 0.37 to 0.56). Cutaneous adverse events were found in 11.9% and 15.6% of participants treated with ivermectin and permethrin, respectively.

Conclusions: The results of this cluster randomised trial of classic scabies, confirmed by dermoscopy, did not show the non-inferiority of oral ivermectin compared with 5% permethrin cream, given on days 0 and 10, in achieving clinical cure of scabies on day 28 in index cases and their household members. Conversely, the trial showed the statistical superiority of 5% permethrin cream.

Trial registration: NCT02407782.

Fig 1

Flowchart of participants enrolled in Scabies Randomised Trial in Children and Adults (SCRATCH). 48 participants in the ivermectin arm and 44 participants in the permethrin arm weighed <15 kg. All children weighing <15 kg received topical 5% permethrin, regardless of the randomisation arm. Participants whose consent forms did not satisfy the regulatory framework were excluded from the analyses

Fig 2

Difference in cure rate between oral ivermectin and topical 5% permethrin cream. The x axis reports the cure rate difference (ivermectin v permethrin) with the associated 95% confidence interval. The lower bound of the confidence interval did not exceed the −10% margin, meaning that ivermectin non-inferiority was not shown. Hence exploration of ivermectin superiority to permethrin was unnecessary. The upper bound of the confidence interval was below 0, however, meaning that permethrin was statistically superior to ivermectin